1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
|
#'Query Qtlizer
#'
#'@description Query Qtlizer database for expression quantitative
#'trait loci (eQTLs) in human.
#'
#'@param query The query consists of search terms and can be a single
#'string or a vector. Qtlizer allows to query both variants
#'(Rsid, ref_version:chr:pos) and genes (Symbol consisting of letters
#'and numbers according to the HGNC guidelines). The minimum allowed character length per search term is 2.
#'@param corr Linkage disequilibrium based on 1000 Genomes Phase 3 European.
#'If this optional value between 0 and 1 is set,
#'the input variants are enriched for proxy variants passing the threshold.
#'Default value is NA.
#'@param max_terms Number of terms in a single HTTP request. Default value is 5.
#'A large value can lead to a very large result set and a error by the database.
#'@param ld_method There are two methods available: "r2" (default) and "dprime".
#'@param ref_version Two possible versions are supported: hg19 (GRCh37) or
#'hg38 (GRCh38). Default value is "hg19".
#'This argument is only considered if a GenomicRanges::GRanges object is returned.
#'@param return_obj The user can choose to get the QTL data to be returned
#'as data frame or as a GenomicRanges::GRanges object. The default value is "dataframe".
#'@return Data frame or GenomicRanges::GRanges object containing QTL data.
#'@examples get_qtls("rs4284742")
#'get_qtls(c("rs4284742", "DEFA1"))
#'get_qtls("rs4284742,DEFA1")
#'get_qtls("rs4284742", return_obj="granges", ref_version="hg38")
#'get_qtls("rs4284742", corr=0.6)
#'@export
get_qtls = function(query, corr = NA, max_terms = 5, ld_method = "r2",
ref_version = "hg19", return_obj = "dataframe"){
# Check if there is an internet connection
if (!curl::has_internet())
stop("No internet connection detected...")
# Split terms
query = paste(query, sep = ' ', collapse = ' ')
query = unique(unlist(strsplit(query, "[\\n\\s,\\t.;]+", perl=TRUE)))
query = query[stringi::stri_length(query)>1]
message(length(query)," unique query term(s) found")
# Binningtolower
bins = vector_split(query, ceiling(length(query)/max_terms))
bins = stringi::stri_join_list(bins, sep = ",")
# Communicate with database
message("Retrieving QTL information from Qtlizer...")
res = lapply(bins, communicate, corr = corr, ld_method = ld_method)
res = do.call(rbind, res)
if(!is.null(res)){
message(nrow(res), " data point(s) received")
} else {
return(res)
}
# Convert to respective data types
res[res == "-"] = NA
if(all(c("p", "distance", "n_qtls", "n_best", "n_sw_sign", "n_occ") %in% names(res))){
res$distance = as.numeric(res$distance)
res$p = as.numeric(res$p)
res$n_qtls = as.numeric(res$n_qtls)
res$n_best = as.numeric(res$n_best)
res$n_sw_sign = as.numeric(res$n_sw_sign)
res$n_occ = as.numeric(res$n_occ)
}
# Create GRanges container
if(tolower(return_obj) == "granges"){
if(tolower(ref_version) == "hg19" || tolower(ref_version) == "grch37"){
# Check for missing hg19 positions
res_with_hg19 = res[which(!is.na(res$var_pos_hg19)),]
if(nrow(res_with_hg19) < nrow(res)){
message("Not all results in GRanges object included due to missing hg19 (GRCh37) positions. Please use set ref_version to hg38 (GRCh38) andd/or set return_obj to 'dataframe' to obtain all results.")
}
gres = GenomicRanges::makeGRangesFromDataFrame(res_with_hg19, start.field = "var_pos_hg19", end.field = "var_pos_hg19",
seqnames.field = "chr", keep.extra.columns = TRUE)
} else {
gres = GenomicRanges::makeGRangesFromDataFrame(res, start.field = "var_pos_hg38", end.field = "var_pos_hg38",
seqnames.field = "chr", keep.extra.columns = TRUE)
}
GenomicRanges::strand(gres) = "+"
comment(gres) = comment(res)
return(gres)
} else {
return(res)
}
}
#'URL building and request/response handling
#'@param q The qtlizer query. Can either be a single string or a vector.
#'@param corr Linkage disequilibrium based on 1000 Genomes Phase 3 European.
#' Optional value between 0 and 1. Default value is NA.
#'@param ld_method There are two methods. Default method is "r2".
#'The other opportunity is to use "dprime".
#'@return Data frame with results.
#'@keywords internal
communicate = function(q, corr, ld_method, n.tries=2){
# Build URL
url = paste0('http://161.97.150.91/rest/qtlizer?q=', q)
if(is.numeric(corr) && corr>=0 && corr<=1){
url = paste0(url, "&corr=", round(corr, digits=2))
if(is.character(ld_method) && (ld_method == "r2" || ld_method == "dprime")){
url = paste0(url, "&ld_method=", ld_method)
}
}
# Send POST request and retrieve response
while(n.tries > 0){
response = httr::POST(url)
if(!httr::http_error(response)){
break
}
Sys.sleep(3)
n.tries = n.tries-1
}
if(n.tries == 0){
stop("Web server seems to be down. Try again later!")
}
result = httr::content(response)
result = unlist(strsplit(result , "\n"))
# Display error message from server
if(length(grep("^#", result)) == 0){
warning(result)
return()
}
# Extract
meta = grep("^#", result, value = TRUE)
data = grep("^[^#]", result, value = TRUE)
# If no QTLs were found
if(length(data)-1 <= 0) {
message("No QTLs found")
return()
}
# Convert to dataframe
header = unlist(strsplit(data[1], "\t"))
ncols = length(header)
data = unlist(strsplit(data[-1], "\t"))
m = matrix(data, ncol=ncols, byrow=TRUE)
d = as.data.frame(m, stringsAsFactors=FALSE)
colnames(d) = header
comment(d) = meta
return(d)
}
#'Splits vector v into n subvectors
#'@param v input vector
#'@param n number of subvectors
#'@return List with subvectors.
#'@keywords internal
vector_split = function(v, n) {
l = length(v)
r = l/n
return(lapply(seq_len(n), function(i){
s = max(1, round(r*(i-1))+1)
e = min(l, round(r*i))
return(v[s:e])
}))
}
|
